This Article Full Text Full Text (PDF) All Versions of this Article: 22/7/1136    most recent 01.ATV.0000022167.80130.A6v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ng, M. K.C. Articles by Celermajer, D. S. Search for Related Content PubMed PubMed Citation Articles by Ng, M. K.C. Articles by Celermajer, D. S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CHORIONIC GONADOTROPIN TESTOSTERONE

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1136.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Prospective Study of Effect of Androgens on Serum Inflammatory Markers in Men

Martin K.C. Ng; Peter Y. Liu; Andrew J. Williams; Shirley Nakhla; Lam P. Ly; David J. Handelsman; David S. Celermajer

From the Department of Cardiology (M.K.C.N., D.S.C.), Royal Prince Alfred Hospital and The Heart Research Institute (M.K.C.N., S.N., D.S.C.); the Department of Andrology (P.Y.L., L.P.L., D.J.H.), Concord Hospital; ANZAC Research Institute (P.Y.L., D.J.H.); the Department of Clinical Immunology (A.J.W.), Royal Prince Alfred Hospital; and the University of Sydney (D.J.H., D.S.C.), Sydney, Australia.

Correspondence to Prof David S. Celermajer, Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW 2050, Australia. E-mail davidc{at}card.rpa.cs.nsw.gov.au

Objective— Because male sex is an independent risk factor for the severity of atherosclerosis, it is possible that androgens may be proatherogenic. There is evidence that sex hormones, particularly estrogens, regulate (or modulate) inflammation, a process integral to atherogenesis. Because levels of serum inflammatory markers predict cardiovascular outcomes, we prospectively assessed the effects of androgen therapy on these markers in older men.

Methods and Results— Levels of high-sensitivity C-reactive protein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured from sera collected at baseline and at the end of 2 randomized double-blind placebo-controlled trials evaluating the effects of 3 months of androgen treatment with either dihydrotestosterone (DHT) or recombinant human chorionic gonadotropin (rhCG) in healthy men aged >60 years with partial androgen deficiency (serum testosterone levels <15 nmol/L). For the DHT study (70 mg transdermally daily), 33 men completed 3 months of treatment (16 men were treated with DHT, and there were 17 controls). For the rhCG (250 µg twice weekly) study, 20 men were treated with rhCG, and there were 20 controls. In both studies, groups were well matched for age and vascular risk factors. Androgen levels (DHT and testosterone) were consistently maintained at eugonadal levels throughout the trials, with estradiol markedly increased by rhCG but not DHT. Baseline CRP levels were 0.74 to 1.49 mg/L, sVCAM-1 levels were 847 to 950 ng/mL, and sICAM-1 levels were 256 to 292 ng/mL in all groups. Neither DHT nor rhCG resulted in significant changes in CRP, sVCAM-1, or sICAM-1 compared with placebo (P>0.3 in both studies).

Conclusions— Exogenous androgen therapy with or without increased estradiol levels does not alter serum inflammatory markers in older men; this finding is in contrast to the effects of estrogens on inflammatory markers that have been found in postmenopausal women. These data provide a measure of reassurance concerning potential adverse cardiovascular effects of androgen therapy in older men.

Key Words: inflammation • testosterone • estrogen • atherosclerosis

This article has been cited by other articles:

				D Kapoor, S Clarke, R Stanworth, K S Channer, and T H Jones The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes Eur. J. Endocrinol., May 1, 2007; 156(5): 595 - 602. [Abstract] [Full Text] [PDF]

				K. H. C. Wu, A. G. Tan, E. Rochtchina, E. J. Favaloro, A. Williams, P. Mitchell, and J. J. Wang Circulating Inflammatory Markers and Hemostatic Factors in Age-Related Maculopathy: A Population-Based Case-Control Study Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 1983 - 1988. [Abstract] [Full Text] [PDF]

				P. Y. Liu, R. C. Christian, M. Ruan, V. M. Miller, and L. A. Fitzpatrick Correlating Androgen and Estrogen Steroid Receptor Expression with Coronary Calcification and Atherosclerosis in Men without Known Coronary Artery Disease J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1041 - 1046. [Abstract] [Full Text] [PDF]

				C. J. Malkin, P. J. Pugh, R. D. Jones, D. Kapoor, K. S. Channer, and T. H. Jones The Effect of Testosterone Replacement on Endogenous Inflammatory Cytokines and Lipid Profiles in Hypogonadal Men J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3313 - 3318. [Abstract] [Full Text] [PDF]

				M. Muller, Y. T. van der Schouw, J. H. H. Thijssen, and D. E. Grobbee Endogenous Sex Hormones and Cardiovascular Disease in Men J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5076 - 5086. [Abstract] [Full Text] [PDF]

				T. B. Ledue and N. Rifai Preanalytic and Analytic Sources of Variations in C-reactive Protein Measurement: Implications for Cardiovascular Disease Risk Assessment Clin. Chem., August 1, 2003; 49(8): 1258 - 1271. [Abstract] [Full Text] [PDF]

				S. Bhasin and K. Herbst Testosterone and Atherosclerosis Progression in Men Diabetes Care, June 1, 2003; 26(6): 1929 - 1931. [Full Text] [PDF]